Identification and validation of hub genes in uterine corpus endometrioid carcinoma: An observational study from TCGA and GEO

子宫内膜样癌中枢基因的鉴定与验证:一项基于TCGA和GEO数据库的观察性研究

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Abstract

Uterine corpus endometrioid carcinoma (UCEC) is a prevalent malignant tumor of the female reproductive system. Despite advancements in molecular biology and treatment strategies, the underlying molecular mechanisms of UCEC tumorigenesis remain incompletely understood. This study aimed to identify differentially expressed genes (DEGs) associated with UCEC pathogenesis, and to determine potential prognostic biomarkers and immunotherapy targets for UCEC. RNA expression datasets and clinical data from UCEC patients were collected from the UCSC Xena database and The Cancer Genome Atlas database. Principal component analysis and LIMMA methods were employed to screen 177 UCEC tissues and 24 normal endometrial tissues. Gene ontology enrichment analysis revealed that up-regulated DEGs were primarily involved in tissue development, cell cycle regulation, and epithelial development. Subsequently, weighted gene co-expression network analysis (WGCNA) identified DEGs in the blue modules that were significantly positively correlated with UCEC, while DEGs in the black modules were significantly negatively correlated with UCEC. Among the identified DEGs through WGCNA, 16 genes were selected, and further Kaplan-Meier analysis demonstrated that 5 of these genes (AURKA, CCNE1, IQGAP3, TTK, and UBE2C) were significantly negatively correlated with overall survival (OS) and considered as hub genes. The expression of these hub genes was validated using GEO datasets and immunohistochemistry (IHC) analysis from the human protein atlas. Additionally, the calculation of immune scores for immune infiltration, immune cell infiltration, and immune cell regulation across the 5 hub genes revealed potential immunotherapeutic targets and strategies. This comprehensive investigation provides insights into the molecular mechanisms underlying UCEC development, identifies 5 promising prognostic biomarkers and immunotherapy targets, and offers guidance for UCEC treatment approaches.

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